Download FORMULATION AND EVALUATION OF BILAYER BUCCAL TABLET OF SUMATRIPTAN SUCCINATE Original Article

Innovare
Academic Sciences
International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491
Vol 6, Issue 6, 2014
Original Article
FORMULATION AND EVALUATION OF BILAYER BUCCAL TABLET OF SUMATRIPTAN
SUCCINATE
SACHIN S. DAREKAR1, S.S. KHADABADI1, S.R. SHAHI1
Government college of Pharmacy Aurangabad, Department of Pharmaceutics, Hotel Vedant Road, osmanpura, Aurangabad, Maharashtra,
India 431005. Email: [email protected]
1
Received: 07 May 2014 Revised and Accepted: 06 Jun 2014
ABSTRACT
Objective: To develop mucoadhesive bilayer buccal tablet of sumatriptan succinate to enhance its bioavailability and reduce its dosing frequency.
Method: A batch prepared with ratio of HPMC K15: HPMC K100LV as 1:3, 4% Penetration enhancer, 40mg backing layer, compressed at 2 tons/cm2
for 10 s was identified as an ideal batch based on its buccal residence time and optimum mucoadhesive strength of 13.99 g. The formulated tablets
were stable with respect to their physicochemical and in vitro drug release behaviour over a period of 60 days at different temperatures and
relative humidity.
Results: The Optimised buccal tablet batch shows the drug release up to 90% in 8hr, good mucoadhesive time as 470 Min.
Conclusion: Mucoadhesive bilayered buccal tablet of sumatriptan succinate may have enhanced bioavailability. A combination of polymer HPMC
K15: HPMC K100LV in the ratio of 1:3 shows good mucoadhesive strength, ex-vivo drug release, and good mucoadhesive time.
Keywords: Bilayer buccal tablet, Sumatriptan succinate, mucoadhesive strength, HPMC K100LV.
INTRODUCTION
Buccal delivery of drug, as an alternative to the oral route of drug
administration, is a subject of growing interest because of its
numerous advantages such as good accessibility, robustness of
epithelium, facile removal of dosage form in case of need, relatively
low enzymatic activity, prevent drug degradation in gastrointestinal
tract and avoid hepatic first-pass metabolism. There are various
dosage forms for buccal drug delivery like buccal tablets, buccal patch,
adhesive gels etc.[1,2] A suitable buccal drug delivery system should
possess good bioadhesive properties, so that it can be retained in the
oral cavity for desired duration. Bioadhesive polymers have been used
extensively for use in buccal drug delivery systems like polyacrylic
acid, polycyanoacrylate, various grades of Hydroxypropyl methyl
cellulose, etc. The development of newer excipients for potential use as
mucoadhesive polymers continues to be of interest. In addition, it
should release the drug in a unidirectional way towards the mucosa, in
controlled and predictable manner, to elicit the required therapeutic
response. This unidirectional drug release can be achieved by using
bilayer devices using polymers like Ethyl cellulose, carbopol,
magnesium separate, polycarbophil, etc. [3,4,5.]
Sumatriptan succinate is 5-HT1receptor agonist used in the
treatment of migraine.
Sumatriptan succinate is chemically
designated as 3-[2-(dimethylamino) ethyl]-N-methyl-indole-5methanesulfonamide succinate. The physiochemical properties of
sumatriptan succinate include its half life about 2.5 hours, molecular
weight about 413, bioavailability 15%(oral), 96%(subcutaneous),
metabolism by MAO-A enzyme.[6]
Migraine is a mysterious disorder characterised by pulsating
headache, usually restricted to one side, which comes in attacks lasting
4-48 hours and is often associated with nausea, vomiting, sensitivity to
light and sound, vertigo, loose motion and other symptoms.[7]
The oral formulation offers convenience and ease of use but produces
unreliable blood levels and inconsistent response. Recurrence
(rebound) occurs with these formulations. This common problem
with recurrence is likely due to persistence of the original event with a
time course exceeding the duration of action from the currently
available formulations. Buccal drug delivery system has the potential
to fill an unmet need in migraine care by providing direct access to the
systemic circulation through the internal jugular vein bypassing the
first pass metabolism leading to high bioavailability. Other advantages
are non-invasive administration, rapid-onset of action, convenient and
easily accessible site, self administrable, low enzymatic activity, etc.
[7,8,9.]
The rationale of this research work is to develop a new
mucoadhesive bilayer buccal tablet of sumatriptan succinate to
counteract the problems associated with the conventional available
marketed preparation of sumatriptan succinate that they have low
bioavailability, frequent dosing as a limitation.
MATERIAL AND METHODS
Sumatriptan succinate (Wockhardt limited MIDC, Waluj,
Aurangabad), HPMC K15M and HPMC K100LV (Colorcon PVT
limited, Goa) were obtained as gift sample. All other chemicals and
reagents used in the work were of analytical grades.
METHODS
Drug identification and drug- excipients compatibility study
Melting Point
Melting point of Sumatriptan Succinate was determined by taking a
small amount of sample in a capillary tube closed at one end and
placed in Digital melting point apparatus. (Veego Digital Melting
point apparatus) The melting point was recorded.
UV Spectrum and Calibration curve of Sumatriptan Succinate
The UV spectrum of Sumatriptan succinate was obtained using
Shimadzu UV1700. Accurately weighed 100 mg of the drug was
dissolved in sufficient quantity of buffer pH 6.8 and volume made
upto100 ml known as stock solution (1000 µg/ml). 1ml of aliquot
was withdrawn and volume was made up to 100 ml using buffer pH
6.8 to obtain the concentration of 10µg/ml (stock 2). Subsequently
aliquots were removed from stock 2 to give 2-10µg/ml. The
resultant solution was scanned from 400 to 200 nm.
Fourier transforms infra-red spectra (FTIR)
The drug sample was placed in FTIR cuvette. The drug sample was
scanned over the range of 4000-400 cm-1 on an FTIR (Prestige 21
SHIMADZU). The FTIR spectra of drug sample were recorded. Similarly,
the procedure repeated by dispersing a sample {drug, drug and polymer
(1:1) as well as mixture of drug and polymers (1:1:1:1) in FTIR cuvette.
Darekar et al.
Differential Scanning Calorimetry (DSC)
Int J Pharm Pharm Sci, Vol 6, Issue 6, 469-475
150mg was then compressed directly using an 11mm diameter die
in a single-stroke multistation tablet machine (Karnavati mini press,
India). Upper punch was raised and the backing layer of ethyl
cellulose was placed on the above compact. Then 2 layers were
compressed into a mucoadhesive bilayer tablet with a total weight of
200 mg/tablet. [10,11.]
The thermal behaviour of Sumatriptan succinate was studied using
Shimadzu DSC TA60 WS Thermal Analyzer. Accurately weighed
samples of (For drug 6.06 mg) were hermetically sealed in
aluminium pan and heated at a constant rate of 20°C/min over
temperature range of 100 to 300°C. The DSC thermo gram was
recorded. The physical mixtures of drug with polymers for
compatibility studies were prepared by triturating drug and drug
and polymers (1:1) in a dried mortar for 5 min and kept as it is for
24 hrs.
Backing Layer
Ethyl cellulose granules were prepared by wet granulation using
isopropyl alcohol as the granulating solvent. The wet mass was
passed through mesh #8 and dried at 40°C for 1 h. The granules
were then passed through mesh #22 and retained on mesh #44. The
core tablet was transferred to the die cavity fitted with 10-mm flat
punch. Ethyl cellulose granules (50 mg) were added and
subsequently compressed at constant maximum compression force.
The tablets were coated from the sides and bottom with ethyl
cellulose as backing membrane such that only the top surface
remained uncoated. [12].
Preparation of BBT of sumatriptan succinate
Core tablet
Various batches of BBT were prepared by changing the ratio of
HPMC K15M, and HPMC K100LV. The drug-polymer combination
was mixed and triturated for 15min (Table 1) in a glass mortar to
obtain homogeneous mixture. The powder mixture equivalent to
Table 1: Formulation of 32Factorial Design Batches
Ingredients (mg) / batch
Sumatriptan succinate
HPMC K15M
HPMC K100LV
SLS
MCC 102
Mg. Stearate
Ethyl cellulose(backing layer)
Total
F1
10
25
80
4
29
2
50
200
F2
10
20
75
4
39
2
50
200
Evaluation of Tablets
Tablets are evaluated for following official and non official tests.
Weight variation test
Twenty tablets were selected at random and weighed individually.
The individual weights were compared with the average weight for
determination of weight variation. [2,5]
Hardness
Tablet hardness is defined as force required to crushing the tablet in
diametric compression test. The hardness was measured with
Monsanto hardness tester. [2,5]
Friability
Twenty tablets were weighed and subjected to friability test in
Roche friabilator. The pre-weighed sample was placed in friabilator
which revolves at 25 rpm for 4 min. dropping the tablets through a
distance of 6 inch with each revolution. This process was repeated
for all formulations and the percentage friability was calculated. [5]
Drug content
Ten tablets were weighed and grounded in a mortar with pestle to
get fine powder. Powder equivalent to the mass of one tablet was
dissolved in ethyl alcohol and filtered through a 0.45-µm filter paper.
The filtrate was diluted with phosphate buffer (pH 6.8).The drug
content was analyzed spectrophotometrically at 227 nm using an UV
spectrophotometer using a reference to a standard calibration curve
of the sumatriptan succinate. [13]
Thickness
The thickness of buccal tablets was determined using a digital
Vernier calliper.
In vitro Drug release studies
USP dissolution apparatus with paddle was used for the in vitro
dissolution studies of mucoadhesive tablets with a simple
modification. A two-end open glass cylinder of 3 cm diameter and 10
cm length was taken. The prepared mucoadhesive tablet was placed
F3
10
25
70
4
39
2
50
200
F4
10
30
75
4
29
2
50
200
F5
10
20
80
4
34
2
50
200
F6
10
30
70
4
34
2
50
200
F7
10
30
80
4
24
2
50
200
F8
10
25
75
4
44
2
50
200
F9
10
20
70
4
44
2
50
200
by applying a moderate pressure onto a moistened membrane
having a thickness of~500µm and this was then tied to one end of
the cylinder, taking care to place the tablet inside the cylinder. This
cylinder was then placed on the surface of dissolution medium (500
ml of phosphate buffer pH 6.8) maintained at 37 ± 0.5 ◦ C at 50 rpm
for 8 h. At specified time intervals, 5 ml samples were withdrawn
and immediately replaced with an equal quantity of fresh buffer. The
samples were filtered and analysed after appropriate dilution by UV
Spectrophotometer at 227 nm. [14, 15.]
Evaluation of mucoadhesive strength
Weight required to pull off the formulation from mucus tissue is
recorded as mucoadhesion/bioadhesion strength in g. This parameter
for the tablets was measured on a modified physical balance using
bovine cheek pouch as model mucosal membrane. [16,3,17]
In-vitro swelling studies
Eight buccal tablets were weighed (W1) and placed separately in
Petri dishes with 5ml of phosphate buffer of pH 6.8. At the time
interval of 1,2,3,4,5,6,7 and 8 hrs, tablets were removed from the
Petri dish and excess water was removed carefully using filter paper.
The swollen tablets were then reweighed (W2) and the percentage
hydration were calculated using the following formula.[18,19,20]
Percentage hydration =
Ex Vivo Mucoadhesion Time
(W2 − W1)
× 100
W1
The ex vivo mucoadhesion time was performed after application of the
buccal tablet on freshly cut sheep buccal mucosa. The fresh sheep
buccal mucosa was tied on the glass slide and a bilayer buccal tablet
core side of each tablet was wetted with 1 drop of phosphate buffer pH
6.8 and pasted to the sheep buccal mucosa by applying a light force
with a fingertip for 30 sec. The glass slide was then put in the beaker,
which was filled with 200 ml of the phosphate buffer pH 6.8 and was
kept at 37 ± 1°C. After 2 min, a 50 rpm stirring rate was applied to
simulate the buccal cavity environment and tablet adhesion was
monitored for 12 h. The time for the tablet to detach from the sheep
buccal mucosa was recorded as the mucoadhesion time. [21,22,23].
470
Darekar et al.
Int J Pharm Pharm Sci, Vol 6, Issue 6, 469-475
Surface pH
UV Spectrum and Calibration curve of Sumatriptan Succinate
A combined glass electrode was used for this purpose. The tablet
was allowed to swell by keeping them in contact with 2 ml of
phosphate buffer pH 6.8 in a test tube for 2hrs.The pH was then
noted by bringing the electrode in contact with the surface of the
formulation pH and allowing it to equilibrate for 1 min.
[24,25,26]
The UV spectrum of Sumatriptan Succinate solution (10µg/ml)
exhibited wavelength of absorbance maximum at 227 nm which
complies with the reported and calibration curve shows r2=0.999.
Statistical analysis by Design Expert Software
A 32 full factorial design was selected and the 2 factors were
evaluated at 3 levels, respectively. The percentages of HPMC K15M
(X1), HPMC k100LV (X2) were selected as independent variables
and the dependent variables were %dr, Mucoadhesive strength,
Mucoadhesive time The data obtained were treated using Stat Ease
Design Expert 7.1.6 software and analyzed statistically using
analysis of variance (ANOVA) . The data were also subjected to 3-D
response surface methodology to study the interaction of HPMC
K15M (X1) HPMC K100LV(X2) on dependent variables.
Kinetics analysis of drug release
To analyze the mechanism of drug release from the tablet the In vitro
dissolution data were fitted to zero order, first order, Higuchi release
model, Hixson and Crowell powder dissolution method and
Korsmeyer Peppas model by using PCP Disso Version 3 software,
and the model with the higher correlation coefficient was considered
to be the best model.
Fig. 1: UV spectrum of Sumatriptan Succinate
RESULTS AND DISCUSSION
Drug Identification and drug-excipients compatibility study
Melting Point
The melting point of Sumatriptan Succinate was determined on
Digital melting point apparatus was found to be 169-172ºC which is
in good agreement with reported melting point.
Fig. 2: Calibration curve of Sumatriptan Succinate
Fourier Transform Infra Red Spectrophotometer (FTIR)
Fig. 3: FTIR spectrum of Sumatriptan Succinate
Fig. 4: FTIR spectrum of Factorial tablet
471
Darekar et al.
Int J Pharm Pharm Sci, Vol 6, Issue 6, 469-475
Differential scanning calorimeter (DSC)
DSC
mW
Temp
C
Thermal Analysis Result
10.00
300.00
0.00
-10.00
File Name:
Detector:
Acquisition Time
Sample Name:
Sample Weight:
Annotation:
SUMA DRUG.tad
DSC60
13:25:05
SUMA DRUG
10.540[mg]
-20.00
Start
168.82 C
End
206.63 C
Peak
184.13 C
Onset
172.26 C
Endset
195.72 C
Heat
-1.02 J
-96.89 x
J/g
Height
-35.66 x
mW
200.00
-30.00
100.00
0.00
2.00
4.00
Time [min]
6.00
Fig. 5: DSC Thermogram of Sumatriptan Succinate
Evaluation of Tablets:
Drug content
The tablets from the factorial batches were evaluated for different
evaluation parameters of tablets.
The drug content of the nine formulations was found to be between
97.2 to102 %( i.e. variation of ±4%).
Appearance
The value ensures good uniformity of the drug content in the tablet.
The tablets from all factorial batches were white, circular. The
surface texture was smooth. The thickness of tablets of factorial
batches was 3.12 to 3.24 mm and it was found to be within limit of
deviation from average value (not more than 5%).
In vitro drug release studies
In vitro drug release study was carried out using USP dissolution
apparatus II in buffer pH 6.8 for a period of 8 Hrs.
Weight variation
Statistical analysis by Design Expert Software
For tablet weighing 300 mg or more, not more than two tablets
differ from the average weight by 5% deviation. The weight
variation within limits indicates uniformity in tablet compression
and consequently content of drug in a unit.
The coefficients of X1 X2 were found to be significant at p <0.05,
hence confirmed the significant effect of all the variables on the
selected responses.
Hardness
3-D Response surface plot
The response surface plots showed that various combinations of
independent variables X1, X2 may satisfy any specific requirement
(i.e. maximum drug release up to 8 hrs and Mucoadhesive strength)
while taking into consideration of various factors involved in dosage
form.
The hardness is important characteristics to be evaluated for
handling and transportation properties of the tablets. The hardness
of tablets was found to be 5.8 to 8.0 Kg/cm2 which indicate good
handling and transportation characteristics.
Friability
Kinetics analysis of drug release
The friability is important characteristics to be evaluated for
handling and transportation properties of the tablets. The friability
of tablets was less than 0.5% which indicates good handling and
transportation characteristics.
DSC
mW
10.00
The various dissolution Models are applied for the kinetics of drug
release study like zero, first, higuchi, peppas model but the best fit model
that follows by all the batches is higuchi (matrix) model.
Temp
C
Thermal Analysis Result
File Name:
Detector:
Acquisition Time
Sample Name:
Sample Weight:
Annotation:
P2 DRUG+POLY.tad
DSC60
17:35:15
P2 DRUG+POLY
7.500[mg]
300.00
5.00
0.00
Start
169.48 x
C
End
198.87 x
C
Peak
181.61 x
C
Onset
172.64 x
C
Endset
193.41 x
C
Heat
-287.63 mJ
-38.35 J/g
Height
-14.28 mW
200.00
100.00
-5.00
0.00
2.00
Time [min]
4.00
6.00
Fig. 6: DSC Thermogram of Tablet blend
472
Darekar et al.
Int J Pharm Pharm Sci, Vol 6, Issue 6, 469-475
Table 2: Evaluation of Bilayer buccal tablet of Sumatriptan Succinate tablets
Batch
Surface
pH
F1
F2
F3
F4
F5
F6
F7
F8
F9
6.58±0.27
6.66±0.2
6.4±0.2
6.1±0.1
6.53±0.15
6.1±0.5
5.86±0.11
6.23±0.05
6.4±0.1
Weight
variation*
mg ± SD
198.66±1.15
199.33±0.57
200±1.0
199.66±0.5
198.66±0.56
200.3±0.57
200±1.0
199.66±0.57
200.33±0.57
All values are mean ± SD n=3
Hardness
(Kg/cm2)
±SD
6.26±0.05
6.56±0.02
6.6±0.1
6.6±0.05
6.2±0.1
6.46±0.05
6.03±0.1
5.93±0.05
5.9±0.1
Friability#
%
Mucoadhesive
time(min)
Thickness
(mm) ±SD
Swelling
index
Mucoadhesive
strength(gm)
0.56±0.005
0.72±0.01
0.65±0.01
0.6±0.1
0.50±0.01
0.56±0.01
0.71±0.02
0.82±0.02
0.77±0.02
325
350
380
410
430
460
470
482
490
2.39±0.02
2.4±0.01
2.42±0.005
2.38±0.005
2.39±0.01
2.38±0.01
2.37±0.0
2.35±0.1
2.39±0.005
19±0.8
29±1.2
45±1.3
52±0.9
56±1.4
59±1.8
62±1.5
61±1.4
67±1.1
5±0.3
7±0.6
9±0.5
7±0.4
8±0.5
12±0.4
13±0.5
15±0.3
11±0.4
Drug
content
(%mg) ±SD
99.43±1.42
99.1±0.6
101.33±0.70
99.06±0.30
99.96±1.35
101.2±0.8
98.5±0.9
99.86±1.25
100.46±1.44
Table 3: Percent total drug release of formulation F1 to F9
Time (Hrs)
1
2
3
4
5
6
7
8
F1
29.4
±0.10
40.65±0.09
52.55
±1.44
64.35±1.40
65.7
±1.50
75.95
±1.13
81.2
±1.32
87.9
±1.40
All values are mean ± SD n=3
F2
39.1
±0.03
45.95±0.10
59.1
±0.04
65.28±0.02
71.7
±0.09
75.4
±0.08
77.9
±0.27
82.4
±0.35
F3
38.5
±0.06
46.2±0.09
56.25
±1.43
62.5±1.53
66.45
±1.37
77.77
±1.27
84.6±1.20
86.05
±1.22
F4
24.65
±0.14
34.35±0.13
47.9
±0.01
54.65±0.12
55.5
±0.05
57.6
±0.08
62.77±0.02
75
±0.24
Drug Release (%)
F5
F6
34.4
32.95
±0.12
±0.05
53.3±0.06
49.2±0.11
60
53.5
±0.07
±0.15
62.32±0.19
58.6±0.10
64.36
60.9
±0.20
±0.22
68.55
63.4
±0.16
±0.11
71.40±0.12
66.20±0.38
76.31
±0.60
72.91
±0.25
F7
32.05
±0.07
48.35±0.12
54.5
±0.14
58.8±0.24
64.7
±0.03
78.5
±0.15
81.5±0.17
90
±0.01
F8
21.1
±0.04
42.6±0.11
49.7
±0.05
55.2±0.05
60
±0.19
62.9
±0.08
75 ±0.06
77.9
±0.22
F9
12.7
±0.07
19.3±0.14
30.2
±0.13
33.5 ±0.37
49.5
±0.03
52.02
±0.07
62.3 ±0.34
64.2
±0.25
Table 4: Analysis of variance for % Drug Release
source
Sum of squares
Df
Mean square
F value
Model
A-HPMC K15
B-HPMC K100LV
Residual
Core Total
387.54
207.68
179.85
154.20
541.74
2
1
1
6
8
193.77
207.68
179.85
25.70
7.54
8.08
7.00
P value
Prob>F
0.0231
0.0295
0.0383
significant
Table 5: Analysis of variance for Mucoadhesive Strength
source
Sum of squares
df
Mean square
F value
Model
A-HPMC K15
B-HPMC K100LV
Residual
Core Total
30.17
13.50
16.67
1.39
31.56
2
1
1
6
8
15.08
13.50
16.67
0.23
65.16
58.32
72.00
P value
Prob>F
< 0.0001
0.0003
Significant
Table 6: Analysis of variance for Mucoadhesive Time
source
Sum of squares
df
Mean square
F value
Model
A-HPMC K15
B-HPMC K100LV
Residual
Core Total
27565.67
2604.17
24961.50
971.22
28536.89
2
1
1
6
8
13782.83
2604.17
24961.50
161.87
85.15
16.09
154.21
P value
Prob>F
< 0.0001
0.0070
< 0.0001
Significant
473
Darekar et al.
Int J Pharm Pharm Sci, Vol 6, Issue 6, 469-475
ACKNOWLEDGEMENTS
The authors are grateful to Wockhardt limited Waluj, Aurangabad
for providing Sumatriptan Succinate as gift sample and Dr. S.S.
Khadabadi Principal Government College of Pharmacy, Aurangabad
for necessary support and valuable guidance.
REFERENCES
1.
2.
3.
Fig. 7: Response Surface Plot for % Drug Release
4.
5.
6.
7.
8.
9.
10.
Fig. 8: Response Surface Plot For Mucoadhesive Strength
11.
12.
13.
14.
15.
16.
Fig. 9: Response Surface Plot For Mucoadhesive Time
CONCLUSION
The bilayer buccal tablet of sumatriptan succinate was prepared. A
combination of polymer HPMC K15: HPMC K100LV in the ratio of
1:3 shows good mucoadhesive strength, ex-vivo drug release, and
good mucoadhesive time. Addition of sodium lauryl sulphate is
useful for the desired permeation across the buccal mucosa. The
preparation of bilayer buccal tablet of sumatriptan succinate shows
increase in the bioavailability thus avoiding the hepatic first pass
effect. The patients get advantages of the buccal tablet for the
treatment of migraine as marketed preparation shows erratic drug
absorption.
17.
18.
19.
20.
Lachman L, Liberman HA. The Theory and Practice of Industrial
Pharmacy. 293-330.
Ansel H, Nicholas G. Pharmaceutical dosage forms and drug
delivery system. 9th edition Lippincott Williams and Wilkins:22537.
Lopez C, Portero A, Jato J. R, Design and evaluation of chitosan /
Ethylcellulose mucoadhesive bilayered devices for buccal drug
delivery,
Journal
of
Controlled
Release.
AAPS
PharmSciTech;55(1998):143-52.
Grabovac V, Guggi D, Bernkop-Schnürch A. Comparison of the
mucoadhesive properties of various polymers. Advanced drug
delivery reviews 2005;57(11):1713-23.
Indian pharmacopeia, controller of publication, government of
India, ministry of health and family welfare, New Delhi Vol.
3;2010:454-5.
Tripathi KD. Essential of medical pharmacology, jaypee brother
medical publisher’s pvt.
Aulton M. E, Pharmaceutics the science of dosage form design,
Churchill Livingston, 2nd edition. AAPS PharmSciTech:413-4.
Gowthamarajan K, Jawahar N, Wake P, Jain K, Sood S.
Development of buccal tablets for curcumin using Anacardium
occidentale
gum,
Carbohydrate
Polymers.
AAPS
PharmSciTech;88(2012):1177-83.
Ching HS, Park H, Kelly P, Robinson JR. Bioadhesive polymers
as platform for oral controlled drug delivery. II Synthesis and
evaluation of some swelling waterinsoluble bioadhesive
polymers Journal of Pharmaceutical Sciences;74:399-405.
Burgalassi S, Panichi L, Saettone MF, Jacobden J, Rassing MR.
Development and in vitro/in vivo testing of mucoadhesive
buccal patches releasing benzylamine and lidocaine.
International Journal of Pharmaceutics 1996;133:1-7.
Park CR, Munday DL. Development and evaluation of a biphasic
buccal adhesive tablet for nicotine replacement therapy.
International journal of pharmaceutics 2002;237(1-2):215-26.
Shidhaye SS, Thakkar PV, Dand NM, Kadam VJ. Buccal drug
delivery of pravastatin sodium. AAPS PharmSciTech
2010;11(1):416-24.
Hassan N, Khar RK, Ali M, Ali J. Development and evaluation of
buccal bioadhesive tablet of an anti-emetic agent ondansetron.
AAPS PharmSciTech 2009;10(4):1085-92.
Bain D. F, Patent No. WO 037814 A1 Bilayered buccal tablets
comprising nicotine 2001.
Alur HH, Pather SI, Mitra AK, Johnston TP. Transmucosal sustaineddelivery of chlorpheniramine maleate in rabbits using a novel,
natural mucoadhesive gum as an excipient in buccal tablets.
International journal of pharmaceutics 1999;188(1):1-10.
Kianfar F, Antonijevic M, Chowdhry B, Boateng JS. Lyophilized
wafers comprising carrageenan and pluronic acid for buccal
drug delivery using model soluble and insoluble drugs. Colloids
and surfaces. B, Biointerfaces 2013;103:99-106.
Rosa B, Giannini L, Rotonda M, Mensitieri G, Miro A, Quaglia F.
Roberto Russo Cyclodextrin-containing poly(ethylene oxide)
tablets for the delivery of poorly soluble drugs: Potential as
buccal delivery system International Journal of Pharmaceutics.
AAPS PharmSciTech;319(2006):63-70.
Pallaprola M, Gowthamarajan K, Jawahar S. Design and
development of buccal drug delivery system for labetalol using
natural polymer, ijprd,; vol. :6; may. AAPS PharmSciTech
2011;3(3):37-49.
Mohana K, Srivalli R, Lakshmi P, Balasubramaniam J. K, Design
of a novel bilayered gastric mucoadhesive system for localized
and unidirectional release of lamotrigine Saudi Pharmaceutical
Journal. AAPS PharmSciTech 2012.
Tsutsumi K, Obata Y, Nagai T, Loftsson T, Takayama K. Buccal
absorption of ergotamine tartrate using the bioadhesive tablet
system in guinea-pigs. International journal of pharmaceutics
2002;238(1-2):161-70.
474
Darekar et al.
21. Shiledar RR, Tagalpallewar AA, Kokare CR. Formulation and in
vitro evaluation of xanthan gum-based bilayered mucoadhesive
buccal patches of zolmitriptan. Carbohydrate polymers
2014;101:1234-42.
22. Kumar K, Velmurugan S. formulation and in vitro evaluation of
glipizide mucoadhesive buccal tablets int j pharm bio Sci. Apr
PN 2013;4(2):594-607.
23. Nair AB, Kumria R, Harsha S, Attimarad M, Al-Dhubiab BE,
Alhaider IA. In vitro techniques to evaluate buccal films. Journal
of controlled release : official journal of the Controlled Release
Society 2013;166(1):10-21.
Int J Pharm Pharm Sci, Vol 6, Issue 6, 469-475
24. Perioli L, Ambrogi V, Rubini D, Giovagnoli S, Ricci M, Blasi P, et
al. Novel mucoadhesive buccal formulation containing
metronidazole for the treatment of periodontal disease. Journal
of controlled release : official journal of the Controlled Release
Society 2004;95(3):521-33.
25. Chien Y, Lee Y. W, oral mucosal controlled drug delivery of
LHRH by bilayer mucoadhesive systems. J control release
1995;37(3):251-61.
26. Khanna R, Agrawal S, Ahuja A, Indian J. P, Preparation and
evaluation of mucoadhesive buccal tablet of clotrimazole for
oral candida infection. pharm Sci 1997;59:299-305.
475